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COMPARISON OF THE EFFECTS OF TWO AR ANTAGONISTS ON ANDROGEN DEPENDENT TISSUES WEIGHTS AND HORMONE LEVELS IN MALE RATS AND ON EXPRESSION OF THREE ANDROGEN DEPENDENT GENES IN THE VENTRAL PROSTATE
Citation:
Wilson, V S., C R. Wood, G A. Held, C R. Lambright, J S. Ostby, J. R. Furr, AND L E. Gray Jr. COMPARISON OF THE EFFECTS OF TWO AR ANTAGONISTS ON ANDROGEN DEPENDENT TISSUES WEIGHTS AND HORMONE LEVELS IN MALE RATS AND ON EXPRESSION OF THREE ANDROGEN DEPENDENT GENES IN THE VENTRAL PROSTATE. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
Comparison of the effects of two AR antagonists on tissue weights and hormone levels in male rats and on expression of three androgen dependent genes in the ventral prostate
VS Wilson, CR Wood, GA Held, CS Lambright, JS Ostby, JR Furr, LE Gray Jr. US EPA, ORD, NHEERL, RTD, RTP, NC
The fungicides vinclozolin (V) and procymidone (P) are AR antagonists that alter androgen-dependent genes in vitro and induce antiandrogenic effects in vivo. V has been shown to alter AR-dependent genes; increasing TRPM-2 (testosterone repressed prostatic message) and repressing C3 (prostatein subunit C3) mRNA levels in vivo. The goal of this study was to determine if adult male rats exposed to P display effects similar to V on TRPM-2, C3 and AR message levels using real time reverse transcription polymerase chain reaction (QPCR). An extension of this study using microarray analysis is presented separately (Rosen, et al., 2003 SOT). Castrated SD rats (72) were assigned to treatments: corn oil vehicle + testosterone implant (T), oral V (200 mg/kg/d) + T implant (VT), oral P (200 mg/kg/d) + T implant (PT) and vehicle with an empty implant (Oil). Rats were necropsied after 20 hr, 4 days, and 7 days. Blood was collected for T and LH, organs were weighed and a portion of the ventral prostate (VP) was fixed for immunohistochemistry. RNA was extracted from ventral prostate (VP) tissue and TRPM-2, C3, and AR quantified using QPCR. As expected, castrate (Oil), VT, and PT decreased androgen dependent tissue weights and increased serum LH. Serum T levels did not differ among the T, VT and PT groups. TRPM-2 was increased at all time points in Oil, VT and PT groups versus the T controls. At 7 days, C3 mRNA levels were reduced in the Oil, VT and PT groups (significant for Oil only). In contrast to the AR mRNA levels, which were elevated, immunohistochemical evaluation indicated that AR protein was reduced by castration. These results indicate that VT and PT produce nearly identical morphological, endocrine and molecular alterations of androgen-dependent processes, which are similar to, but less robust than those produced by elimination of T by castration. Abstract of a proposed presentation and does not necessarily reflect EPA policy